PMID- 35977348
OWN - NLM
STAT- MEDLINE
DCOM- 20220819
LR  - 20220911
IS  - 2473-4284 (Electronic)
IS  - 2473-4284 (Linking)
VI  - 6
DP  - 2022 Aug
TI  - Tumor Mutational Burden as a Predictor of First-Line Immune Checkpoint Inhibitor 
      Versus Carboplatin Benefit in Cisplatin-Unfit Patients With Urothelial Carcinoma.
PG  - e2200121
LID - 10.1200/PO.22.00121 [doi]
AB  - PURPOSE: In real-world settings, patients with metastatic urothelial carcinoma 
      (mUC) are often more frail than clinical trials, underscoring an unmet need to 
      identify patients who might be spared first-line chemotherapy. We sought to 
      determine whether tumor mutational burden (TMB) identifies patients with 
      comparable or superior clinical benefit of first-line single-agent immune 
      checkpoint inhibitors (ICPI) in real-world patients deemed cisplatin-unfit. 
      METHODS: Patients with mUC treated in first-line advanced setting (N = 401) 
      received ICPI (n = 245) or carboplatin regiment without ICPI (n = 156) at 
      physician's discretion in standard-of-care settings across approximately 280 US 
      academic or community-based cancer clinics between March 2014 and July 2021. 
      Deidentified data were captured into a real-world clinicogenomic database. All 
      patients underwent testing using Foundation Medicine assays. Progression-free 
      survival (PFS), time to next treatment (TTNT), and overall survival (OS) 
      comparing ICPI versus chemotherapy were adjusted for known treatment assignment 
      imbalances using propensity scores. RESULTS: TMB >/= 10 was detected in 122 of 401 
      (30.4%) patients. Among patients receiving ICPI, those with TMB >/= 10 had more 
      favorable PFS (HR, 0.59; 95% CI, 0.41 to 0.85), TTNT (HR, 0.59; 95% CI, 0.43 to 
      0.83), and OS (HR, 0.47; 95% CI, 0.32 to 0.68). Comparing ICPI versus 
      carboplatin, adjusting for imbalances, patients with TMB >/= 10 had more favorable 
      PFS (HR, 0.51; 95% CI, 0.32 to 0.82), TTNT (HR, 0.56; 95% CI, 0.35 to 0.91), and 
      OS (HR, 0.56; 95% CI, 0.29 to 1.08) on ICPI versus chemotherapy, but not TMB < 
      10. Comparisons unadjusted for imbalances had similar associations. CONCLUSIONS: 
      In real-world settings, mUC patients with TMB >/= 10 have more favorable outcomes 
      on first-line single-agent ICPI than carboplatin, adding clinical validity to TMB 
      assessed by an existing US Food and Drug Administration-approved platform.
FAU - Graf, Ryon P
AU  - Graf RP
AUID- ORCID: 0000-0002-8065-4148
AD  - Foundation Medicine, Cambridge, MA.
FAU - Fisher, Virginia
AU  - Fisher V
AD  - Foundation Medicine, Cambridge, MA.
FAU - Huang, Richard S P
AU  - Huang RSP
AUID- ORCID: 0000-0001-8395-5168
AD  - Foundation Medicine, Cambridge, MA.
FAU - Hamdani, Omar
AU  - Hamdani O
AUID- ORCID: 0000-0001-6889-8572
AD  - Foundation Medicine, Cambridge, MA.
FAU - Gjoerup, Ole V
AU  - Gjoerup OV
AUID- ORCID: 0000-0001-9127-8769
AD  - Foundation Medicine, Cambridge, MA.
FAU - Stanke, Jennifer
AU  - Stanke J
AD  - Foundation Medicine, Cambridge, MA.
FAU - Creeden, James
AU  - Creeden J
AD  - Foundation Medicine, Cambridge, MA.
FAU - Levy, Mia A
AU  - Levy MA
AUID- ORCID: 0000-0002-5944-2730
AD  - Foundation Medicine, Cambridge, MA.
AD  - Rush University Medical Center, Chicago, IL.
FAU - Oxnard, Geoffrey R
AU  - Oxnard GR
AUID- ORCID: 0000-0003-1054-8240
AD  - Foundation Medicine, Cambridge, MA.
FAU - Gupta, Shilpa
AU  - Gupta S
AUID- ORCID: 0000-0002-8775-503X
AD  - Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - JCO Precis Oncol
JT  - JCO precision oncology
JID - 101705370
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - BG3F62OND5 (Carboplatin)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Biomarkers, Tumor
MH  - Carboplatin/therapeutic use
MH  - *Carcinoma, Transitional Cell/drug therapy
MH  - Cisplatin/therapeutic use
MH  - Humans
MH  - Immune Checkpoint Inhibitors
MH  - *Urinary Bladder Neoplasms/drug therapy
EDAT- 2022/08/18 06:00
MHDA- 2022/08/20 06:00
CRDT- 2022/08/17 16:06
PHST- 2022/08/17 16:06 [entrez]
PHST- 2022/08/18 06:00 [pubmed]
PHST- 2022/08/20 06:00 [medline]
AID - 10.1200/PO.22.00121 [doi]
PST - ppublish
SO  - JCO Precis Oncol. 2022 Aug;6:e2200121. doi: 10.1200/PO.22.00121.